Whole genome DNA methylation profile of sperm cells in mammalian species

DNA methylation in sperm is among the most important factors shaping evolution of the mammalian genome. By directly altering germline mutation rates, the DNA methylation system has shaped the CpG landscape of mammalian genomes, resulting in the CpG island phenomenon. Yet little is known about how this system itself has co-evolved with its substrate during mammalian evolution. We analyzed full-genome single-CpG DNA methylation profiles in sperm from human, chimp, gorilla, rhesus, mouse, rat and dog. Our results point to an evolutionary expansion of the unmethylated portion of mammalian genomes. Within the mutually orthologous genome this trend is driven both by the birth of unmethylated regions and by widening of intervals that are unmethylated in ancestors. We find strikingly divergent global features in rodents. At the same time, we observe the evolutionary emergence of methylome features in mouse sperm bears association with similar pathways to those found in human. Together,these results revealed general principles in mammalian epigenome evolution.精子DNA甲基化（DNA methylation）是塑造哺乳动物基因组演化的关键因素之一。通过直接改变生殖系突变率，DNA甲基化系统塑造了哺乳动物基因组的CpG景观，进而催生了CpG岛（CpG island）现象。然而，学界对该系统自身如何在哺乳动物演化历程中与其作用底物协同演化，仍知之甚少。我们分析了人类、黑猩猩、大猩猩、恒河猴、小鼠、大鼠与犬的精子全基因组单CpG分辨率DNA甲基化谱。我们的研究结果表明，哺乳动物基因组的非甲基化区域呈现演化扩张趋势。在互为直系同源的基因组区域中，这一趋势由两方面驱动：一是非甲基化区域的新生，二是祖先物种中已存在的非甲基化区间的范围扩大。我们发现啮齿类动物的全局甲基化特征存在显著分化。与此同时，我们观察到小鼠精子中甲基化组（methylome）的新演化特征，与人类中鉴定到的相关通路存在关联。综上，这些研究结果揭示了哺乳动物表观基因组（epigenome）演化的通用原则。